Method for Producing Alkylanilides from Halobenzene Derivatives

ABSTRACT

The present invention relates to a novel process for preparing known fungicidally active alkylanilides from 2-alkylhaloaromatics and heterocyclylamides.

The present invention relates to a process for preparing known fungicidally active alkylanilides from 2-alkylhaloaromatics and heterocyclylamides.

EP-A-0 824 099 and WO-A-03010149 disclose that alkylanilides are obtained by reacting the appropriate acid chloride with the appropriate alkylaniline derivative.

Both preparation and handling of the acid chlorides and the preparation of the alkylanilides are associated with a considerable level of technical complexity. For example, the acid chlorides have to be purified before the reaction by a time-consuming and costly distillation step.

The anilines are prepared typically, as described in WO-A-3074491, by a complicated synthesis from the corresponding bromoaromatics and benzophenone imine or at temperatures of 150° C. and pressures of from 75 to 85 bar with ammonia gas, as described in WO-A-06061226.

Alkylanilines, however, frequently exhibit toxic properties and are potentially mutagenic.

The prior art discloses that aryl halides can be reacted with amides under palladium or copper catalysis to give alkylanilides (J. Am. Chem. Soc. 2002, 124, 7420).

It is frequently found, however, that metal-catalyzed reactions with heterocycles which can function as chelating ligands are inhibited. Furthermore, ortho-substituted haloaromatics are sterically hindered for a halogen exchange.

It is therefore an object of the present invention to provide a process for simple and selective preparation of alkylanilides, which does not have the disadvantages described in the prior art.

Surprisingly, conditions have been found under which heterocyclylamides can be reacted efficiently with ortho-substituted haloaromatics.

The present invention thus provides a process for preparing alkylanilides of the formula (I)

in which

-   -   R¹ is hydrogen, halogen, —CR′ (R′=hydrogen, fluorine or         O—C₁₋₄-alkyl), more preferably hydrogen;     -   R² is —CH(Me)—CH₂—CHMe₂, —CH₂—CH₂-t-But, or

-   -    particular preference being given to —CH(Me)—CH₂—CHMe₂ and

-   -   A is the radical of the formula (A1)

in which

-   -   R³ is hydrogen, cyano, halogen, nitro, C₁-C₄-alkyl,         C₁-C₄-alkoxy, C₁-C₄-alkylthio, C₃-C₆-cycloalkyl,         C₁-C₄-haloalkyl, C₁-C₄-haloalkoxy or C₁-C₄-haloalkylthio having         in each case from 1 to 5 halogen atoms, aminocarbonyl or         aminocarbonyl-C₁-C₄-alkyl;     -   R⁴ is hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-alkoxy or         C₁-C₄-alkylthio;     -   R⁵ is hydrogen, C₁-C₄-alkyl, hydroxy-C₁-C₄-alkyl, C₂-C₆-alkenyl,         C₃-C₆-cycloalkyl, C₁-C₄-alkylthio-C₁-C₄-alkyl,         C₁-C₄-alkoxy-C₁-C₄-alkyl, C₁-C₄-haloalkyl,         C₁-C₄-haloalkylthio-C₁-C₄-alkyl, C₁-C₄-haloalkoxy-C₁-C₄-alkyl         having in each case from 1 to 5 halogen atoms, or phenyl;         or     -   A is the radical of the formula (A2)

in which

-   -   R⁶ and R⁷ are each independently hydrogen, halogen, C₁-C₄-alkyl         or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms,     -   R⁸ is halogen, cyano or C₁-C₄-alkyl, or C₁-C₄-haloalkyl or         C₁-C₄-haloalkoxy having in each case from 1 to 5 halogen atoms,         or     -   A is the radical of the formula (A3)

in which

-   -   R⁹ and R¹⁰ are each independently hydrogen, halogen, C₁-C₄-alkyl         or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms,     -   R¹¹ is hydrogen, halogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl having         from 1 to 5 halogen atoms,         or     -   A is the radical of the formula (A4)

in which

-   -   R¹² is hydrogen, halogen, hydroxyl, cyano, C₁-C₆-alkyl,         C₁-C₄-haloalkyl, C₁-C₄-haloalkoxy or C₁-C₄-haloalkylthio having         in each case from 1 to 5 halogen atoms,         or     -   A is the radical of the formula (A5)

in which

-   -   R¹³ is halogen, hydroxyl, cyano, C₁-C₄-alkyl, C₁-C₄-alkoxy,         C₁-C₄-alkylthio, C₁-C₄-haloalkyl, C₁-C₄-haloalkylthio or         C₁-C₄-haloalkoxy having in each case from 1 to 5 halogen atoms,     -   R₁₄ is hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-alkoxy,         C₁-C₄-alkylthio, C₁-C₄-haloalkyl, C₁-C₄-haloalkoxy having in         each case from 1 to 5 halogen atoms, C₁-C₄-alkylsulfinyl or         C₁-C₄-alkylsulfonyl,         or     -   A is the radical of the formula (A6)

in which

-   -   R¹⁵ is C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen         atoms,     -   R¹⁶ is C₁-C₄-alkyl,     -   Q¹ is S (sulfur), O (oxygen), SO, SO₂ or CH₂,     -   p is 0, 1 or 2, where R¹⁶ represents identical or different         radicals when p is 2,         or     -   A is the radical of the formula (A7)

in which

-   -   R¹⁷ is C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen         atoms,         or     -   A is the radical of the formula (A8)

in which

-   -   R¹⁸ is C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen         atoms,         or     -   A is the radical of the formula (A9)

in which

-   -   R¹⁹ and R²⁰ are each independently hydrogen, halogen, amino,         C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms,     -   R²¹ is hydrogen, halogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl having         from 1 to 5 halogen atoms,         or     -   A is the radical of the formula (A10)

in which

-   -   R²² and R²³ are each independently hydrogen, halogen, amino,         nitro, C₁-C₄-alkyl or C₁-C₄-haloalkyl having 1 to 5 halogen         atoms,     -   R²⁴ is hydrogen, halogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl having         from 1 to 5 halogen atoms,         or     -   A is the radical of the formula (A11)

in which

-   -   R²⁵ is hydrogen, halogen, amino, C₁-C₄-alkylamino,         di(C₁-C₄-alkyl)amino, cyano, C₁-C₄-alkyl or C₁-C₄-haloalkyl         having from 1 to 5 halogen atoms,     -   R26 is halogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to         5 halogen atoms,         or     -   A is the radical of the formula (A12)

in which

-   -   R²⁷ is hydrogen, halogen, amino, C₁-C₄-alkylamino,         di(C₁-C₄-alkyl)amino, cyano, C₁-C₄-alkyl or C₁-C₄-haloalkyl         having from 1 to 5 halogen atoms,     -   R²⁸ is halogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to         5 halogen atoms,         or     -   A is the radical of the formula (A13)

in which

-   -   R²⁹ is halogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to         5 halogen atoms,         or     -   A is the radical of the formula (A14)

in which

-   -   R³⁰ is hydrogen or C₁-C₄-alkyl,     -   R³¹ is halogen or C₁-C₄-alkyl,         or     -   A is the radical of the formula (A15)

in which

-   -   R³² is C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen         atoms,         or     -   A is the radical of the formula (A16)

in which

-   -   R³³ is hydrogen, halogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl having         from 1 to 5 halogen atoms,         or     -   A is the radical of the formula (A17)

in which

-   -   R³⁴ is halogen, hydroxyl, C₁-C₄-alkyl, C₁-C₄-alkoxy,         C₁-C₄-alkylthio, C_(l)-C₄-haloalkyl, C₁-C₄-haloalkylthio or         C₁-C₄-haloalkoxy having in each case from 1 to 5 halogen atoms,         or     -   A is the radical of the formula (A18)

in which

-   -   R³⁵ is hydrogen, cyano, C₁-C₄-alkyl, C₁-C₄-haloalkyl having from         1 to 5 halogen atoms, C₁-C₄-alkoxy-C₁-C₄-alkyl,         hydroxy-C₁-C₄-alkyl, C₁-C₄-alkylsulfonyl,         di(C₁-C₄-alkyl)aminosulfonyl, C₁-C₆-alkylcarbonyl or in each         case optionally substituted phenylsulfonyl or benzoyl,     -   R³⁶ is hydrogen, halogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl having         from 1 to 5 halogen atoms,     -   R³⁷ is hydrogen, halogen, cyano, C₁-C₄-alkyl or C₁-C₄-haloalkyl         having from 1 to 5 halogen atoms,     -   R³⁸ is hydrogen, halogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl having         from 1 to 5 halogen atoms,         or     -   A is the radical of the formula (A19)

in which

-   -   R³⁹ is C₁-C₄-alkyl,         characterized in that,

in a first step, carboxamides of the formula (II)

in which the A radical is as defined above

are reacted with haloalkylbenzenes of the formula (III)

in which

the R¹ and R² radicals are each as defined above and the substituent R¹ is preferably in the meta or para position, more preferably in the 4 position (para to X) of the aromatic; and

the X radical is a halogen, preferably Cl or Br, more preferably Br,

in a metal-catalyzed reaction.

The present invention further relates to compounds of the formula (III)

where

-   -   R¹ is hydrogen, halogen, −CR′(CF₃)₂ (R′=hydrogen, fluorine or         O—C₁₋₄-alkyl), more preferably hydrogen, and the substituent R¹         is preferably in the meta or para position, more preferably in         the 4 position (para to X) of the aromatic; and     -   R² is —CH(Me)—CH₂—CHMe₂ and —CH₂—CH₂-t-But,         or     -   R¹ is halogen, —CR′(CF₃)₂ (R′=hydrogen, fluorine or         O-C₁₋₄-alkyl), more preferably hydrogen, and the substituent R¹         is preferably in the meta or para position, more preferably in         the 4 position (para to X) of the aromatic; and     -   R² is

and

-   -   X is a halogen, preferably Cl or Br, more preferably Br.

The present invention additionally relates to the compounds of the formulae (IV) to (VI)

A further aspect of the present invention relates to the use of the compounds of one of the formulae (II), (III), (IV), (V) and (VI) as reactants/intermediates in the process according to the invention described above.

The inventive reaction will be described in detail with reference to scheme (I) below:

In connection with the present invention, the term “halogen” (X) encompasses elements which are selected from the group consisting of fluorine, chlorine, bromine and iodine, preference being given to using chlorine and bromine, and particular preference to using bromine.

Optionally substituted radicals may be mono- or polysubstituted, where the substituents may be the same or different in the case of polysubstitutions.

The definition “C₁-C₆-alkyl” encompasses the largest range for an alkyl radical defined herein. Specifically, this definition encompasses the meanings of methyl, ethyl, n-, isopropyl, n-, iso-, sec-, tert-butyl, and in each case all isomeric pentyls and hexyls.

The definition “C₂-C₆-alkenyl” encompasses the largest range for an alkenyl radical defined herein. Specifically, this definition encompasses the meanings of ethenyl, n-, isopropenyl, n-, iso-, sec-, tert-butenyl, and in each case all isomeric pentenyls and hexenyls.

The inventive compounds can optionally be used as mixtures of different possible isomeric forms, especially of stereoisomers, for example E and Z, threo and erythro, and also optical isomers, and if appropriate also of tautomers. It is possible to use both the E and the Z isomers, and also the threo and erythro isomers, and also the optical isomers, any mixtures of these isomers, and also the possible tautomeric forms.

The haloalkylbenzenes required are known in the prior art, for example from WO-A-03074491, or can be prepared by known methods by Friedel-Crafts alkylation or electrophilic aromatic halogenation.

A further possibility is that of reacting 2-halobenzaldehydes with Wittig reagents, in which case the propenone derivatives thus obtained, as described in WO-A-03074491, can be converted to cyclopropyl compounds.

Other possibilities are the hydroxyalkylation of aromatics or metalated aromatics with ketones or acid chlorides and, respectively, the subsequent elimination and reduction thereof. Proceeding from 1,2-dibromobenzene, this is illustrated by way of example in scheme (II):

Alternatively, it is also possible to obtain the halogen compounds in question from aniline derivatives by diazotization and Sandmeyer reaction.

According to the present invention, the haloalkylbenzene of the formula (IX)

in which X is a halogen atom, especially Br, is a preferred reactant.

Only some of the acid amides required are known, and they can be obtained from known acid halides, acids, esters or nitrites by known reactions.

This will be illustrated by the following example according to scheme (III):

The nitrogen source used may be aqueous or gaseous ammonia or one of its salts, for example ammonium acetate or sodium amide.

Useful solvents for the preparation of the acid amides include all solvents which are stable under the reaction conditions, for example ethers such as THF, 2-methyl-THF, dioxane, methyl t-butyl ether (MTBE), diethylene glycol, diethoxymethane, dimethoxymethane; aromatic hydrocarbons such as toluene, xylene, chlorobenzene, dichlorobenzene, benzene; aliphatic hydrocarbons such as petroleum ether, heptane, hexane, methylcyclohexane, cyclohexane; dimethylformamide (DMF); dimethylacetamide; N-methylpyrrolidone (NMP); dimethyl sulfoxide (DMSO), acetonitrile; butyronitrile; water; ketones such as acetone, methyl isobutyl ketone (MIBK); alcohols such as methanol, ethanol, isopropanol.

For the inventive reaction of the acid amide with the halobenzene derivative, metal catalysts are used. For this purpose, palladium and copper in all oxidation states are useful, for example in metallic form or in the form of salts.

According to the present invention, for example, Pd(OAc)₂, Pd(OH)₂, PdCl₂, Pd(acac)₂ (acac=acetylacetonate), Pd(NO₃)₂, Pd(dba)₂, Pd₂dba₃, (dba=dibenzylideneacetone), dichlorobis(triphenylphosphine)palladium(II), Pd(CH₃CN)₂Cl₂, tetrakis(triphenylphosphine)palladium(0), Pd/C or palladium nanoparticles, CuI, CuCl, CuSCN, Cu₂O, CuO, CuCl₂, CuSO₄, CuBr, CuBr₂, Cu₂S, Cu(OAc)₂, Cu(acac)₂ are suitable, preference being given to using the copper compounds or mixtures thereof.

According to the present invention, the catalysts are used in catalytic amounts. This means that the metal catalysts are used in concentrations of from 0.01 to 50.0 mol %, preferably of 1.0 to 20.0 mol %, based on the carboxamides of the formula (II).

The inventive reaction is preferably performed in the presence of ligands.

In the case of palladium catalysis, suitable ligands are, for example, selected from the group of carbene and phosphine ligands, particular preference being given to using xantphos and tris(t-butyl)phosphine.

In the case of copper catalysis, suitable ligands are, for example, selected from the group consisting of diamines, for example N,N′-dimethyl-1,2-cyclohexanediamine (cis or trans, racemic or as an enantiomer), N,N′-dimethylethylenediamine, ethylenediamine, N-methylethylenediamine, N-butylethylenediamine, N,N,N′-trimethylethylenediamine or else 1,10-phenanthroline, ethylenediaminetetraacetic acid, tetra-n-butylammonium fluoride, tris(3,6-trioxaheptyl)amine (TDA-1), particular preference being given to using N,N′-dimethyl-1,2-cyclohexanediamine.

The ligands are added to the metal catalyst in such a ratio that the desired catalytic action occurs.

According to the present invention, the ratio of ligand to metal catalyst is between 0.5 to 10 equivalents, preferably between 1 to 5 equivalents.

The reaction is preferably carried out in the presence of bases. Useful examples include alkali metal and alkaline earth metal hydroxides such as KOH, NaOH, Ca(OH)₂, fluorides such as KF, phosphates such as K₃PO₄, and carbonates such as potash, soda, cesium carbonate or phosphazene bases, alkoxides such as sodium tert-butoxide, or phenoxides such as sodium phenoxide.

According to the present invention, the bases are used in concentrations of from 0.5 to 5 equivalents, preferably from 1.0 to 3 equivalents, based on the carboxamides of the formula (II).

The inventive reaction of the acid amide with the halobenzene derivative is preferably carried out in a solvent.

The solvents used are preferably dioxane, THF, diglyme, toluene, xylene, DMF.

According to the present invention, the acid amides and the halobenzene derivatives are reacted with one another in an equimolar ratio. In an alternative embodiment, the halobenzene derivative can also be used in excess, for example as a solvent.

According to the invention, the acid amides are reacted with the halobenzene derivatives at temperatures in the range from 20 to 200° C., preferably from 70 to 150° C.

In a particularly preferred embodiment of the invention, carboxamides of the formula (V) are reacted with compounds of the formula (X)

in which the X radical is a halogen to give carboxamides of the formula (XI)

The examples which follow are intended to illustrate the subject matter of the invention in detail, but without restricting it thereto.

WORKING EXAMPLES

1-Bromo-2-(1,3-dimethylbutyl)benzene

28.4 g of 2-(1,3-dimethylbutyl)aniline in 134.9 g (667 mmol) of 40 percent hydrobromic acid in glacial acetic acid at 10° C. are admixed with 12.5 g (181 mmol) of sodium nitrite in portions with stirring within 1.5 h. Thereafter, 0.5 g of copper powder is added and the mixture is boiled under reflux for 1 h hour. Subsequently, 120 ml of water and sodium hydroxide solution are added until pH 12 is attained, and the organic phase is removed, washed with dilute hydrochloric acid and concentrated by evaporation under reduced pressure. After distillation in a Kugelrohr apparatus at 0.3 mbar/70° C. and purification of the main fraction by means of preparative HPLC, 8.3 g of a yellowish oil with a purity of 99.4% (determined by HPLC) are obtained.

¹H NMR (400 MHz, CDCl₃): 0.89 (dd, 6H), 1.17 (d, 3H), 1.32-1.38 and 1.46-1.53 (2m, AB, 2×1H), 1.54-1.6 (m, 1H), 3.34 (m, 1H), 7 (m, 1H), 7.21-7.28 (m, 2H), 7.52 (d, 1H).

5-Fluoro-1,3-dimethyl-1 H-pyrazole-4-carboxamide

19.9 g of 5-fluoro-1,3-dimethyl-1H-pyrazole-4-carbonyl chloride are added dropwise at 20-35° C. to a mixture of 35 g of 25 percent aqueous ammonia and 170 ml of THF. After stirring for 4 h, the organic solvent fraction is concentrated by evaporation under reduced pressure and 0.2 mol of potash and sodium chloride are added to saturation. After extracting four times with ethyl acetate and concentrating the combined organic phases by evaporation under reduced pressure, 16.6 g of a yellow solid are obtained.

¹H NMR (400 MHz, d⁶-DMSO): 2.64 (s, 3H), 3.63 (s, 3H), 6.9 (broad s, 1H), 7.18 (broad s, 1H).

N-[2-(1,3-Dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide

A mixture of 0.221 g (1.16 mmol) of copper iodide, 3.21 g (23.22 mmol) of potash and 2.189 g of 5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide is admixed under argon with 330 mg (2.322 mmol) of N,N′-dimethyl-1,2-cyclohexanediamine, 2.8 g (11.6 mmol) of 1-bromo-2-(1,3-dimethylbutyl)benzene and 30 ml of toluene. After boiling under reflux for one day, the mixture is poured onto water and 10 ml of a 5% EDTA solution. Subsequently, the mixture is extracted three times with ethyl acetate and concentrated by evaporation under reduced pressure. The oily residue is dissolved in toluene and stirred into n-hexane. After the precipitated crystals have been filtered off with suction, 3.3 g (89% of the theoretical yield) of N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide are obtained with a purity (HPLC) of 99%. 

1. A process for preparing carboxamides of the general formula (I)

in which R¹ is hydrogen, halogen, —CR′ where R′=hydrogen, fluorine or O—C₁₋₄-alkyl;

R² is —CH(Me)—CH₂—CHMe₂, —CH₂—CH₂-t-But or A is the radical of the formula (A1)

in which R³ is hydrogen, cyano, halogen, nitro, C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-alkylthio, C₃-C₆-cycloalkyl, C₁-C₄-haloalkyl, C₁-C₄-haloalkoxy or C₁-C₄-haloalkylthio having in each case from 1 to 5 halogen atoms, aminocarbonyl or aminocarbonyl-C₁-C₄-alkyl; R⁴ is hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-alkoxy or C₁-C₄-alkylthio; R⁵ is hydrogen, C₁-C₄-alkyl, hydroxy-C₁-C₄-alkyl, C₂-C₆-alkenyl, C₃-C₆-cycloalkyl, C₁-C₄-alkylthio-C₁-C₄-alkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-haloalkylthio-C₁-C₄-alkyl, C₁-C₄-haloalkoxy-C₁-C₄-alkyl having in each case from 1 to 5 halogen atoms, or phenyl; or A is the radical of the formula (A2)

in which R⁶ and R⁷ are each independently hydrogen, halogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms, R⁸ is halogen, cyano or C₁-C₄-alkyl, or C₁-C₄-haloalkyl or C₁-C₄-haloalkoxy having in each case from 1 to 5 halogen atoms, or A is the radical of the formula (A3)

in which R⁹ and R¹⁰ are each independently hydrogen, halogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms, R¹¹ is hydrogen, halogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A4)

in which R¹² is hydrogen, halogen, hydroxyl, cyano, C₁-C₆-alkyl, C₁-C₄-haloalkyl, C₁-C₄-haloalkoxy or C₁-C₄-haloalkylthio having in each case from 1 to 5 halogen atoms, or A is the radical of the formula (A5)

in which R¹³ is halogen, hydroxyl, cyano, C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-alkylthio, C₁-C₄-haloalkyl, C₁-C₄-haloalkylthio or C₁-C₄-haloalkoxy having in each case from 1 to 5 halogen atoms, R¹⁴ is hydrogen, halogen, cyano, C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-alkylthio, C₁-C₄-haloalkyl, C₁-C₄-haloalkoxy having in each case from 1 to 5 halogen atoms, C₁-C₄-alkylsulfinyl or C₁-C₄-alkylsulfonyl, or A is the radical of the formula (A6)

in which R¹⁵ is C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms, R¹⁶ is C₁-C₄-alkyl, Q¹ is S (sulfur), O (oxygen), SO, SO₂ or CH₂, p is 0, 1 or 2, where R¹⁶ represents identical or different radicals when p is 2, or A is the radical of the formula (A7)

in which R¹⁷ is C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A8)

in which R¹⁸ is C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A9)

in which R¹⁹ and R²⁰ are each independently hydrogen, halogen, amino, C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms, R²¹ is hydrogen, halogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A10)

in which R²² and R²³ are each independently hydrogen, halogen, amino, nitro, C₁-C₄-alkyl or C₁-C₄-haloalkyl having 1 to 5 halogen atoms, R²⁴ is hydrogen, halogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A11)

in which R²⁵ is hydrogen, halogen, amino, C₁-C₄-alkylamino, di(C₁-C₄-alkyl)amino, cyano, C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms, R²⁶ is halogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A12)

in which R²⁷ is hydrogen, halogen, amino, C₁-C₄-alkylamino, di(C₁-C₄-alkyl)amino, cyano, C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms, R²⁸ is halogen, C₁-C4-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A13)

in which R²⁹ is halogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A14)

in which R³⁰ is hydrogen or C₁-C₄-alkyl, R³¹ is halogen or C₁-C₄-alkyl, or A is the radical of the formula (A15)

in which R³² is C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A16)

in which R³³ is hydrogen, halogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A17)

in which R³⁴ is halogen, hydroxyl, C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-alkylthio, C₁-C₄-haloalkyl, C₁-C₄-haloalkylthio or C₁-C₄-haloalkoxy having in each case from 1 to 5 halogen atoms, or A is the radical of the formula (A18)

in which R³⁵ is hydrogen, cyano, C₁-C₄-alkyl, C₁-C₄-haloalkyl having from 1 to 5 halogen atoms, C₁-C₄-alkoxy-C₁-C₄-alkyl, hydroxy-C₁-C₄-alkyl, C₁-C₄-alkylsulfonyl, di(C₁-C₄-alkyl)aminosulfonyl, C₁-C₆-alkylcarbonyl or in each case optionally substituted phenylsulfonyl or benzoyl, R³⁶ is hydrogen, halogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms, R³⁷ is hydrogen, halogen, cyano, C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms, R³⁸ is hydrogen, halogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl having from 1 to 5 halogen atoms,  or A is the radical of the formula (A19)

in which R³⁹ is C₁-C₄-alkyl, characterized in that, in a first step, carboxamides of the formula (II)

in which the A radical is as defined above are reacted with haloalkylbenzenes of the formula (III)

in which the R¹ and R² radicals are each as defined above and the X radical is a halogen atom in a metal-catalyzed reaction.
 2. The process as claimed in claim 1, wherein carboxamides of the formula (II) which are selected from the group consisting of compounds of the formulae (IV) to (VI)

are converted to carboxamides of the general formula (VIII)

in which the R¹ and R² radicals are each as defined in claim 1, Z is methyl, difluoromethyl or trifluoromethyl and Y is hydrogen, methyl or fluorine.
 3. The process as claimed in either of claims 1 or 2, characterized in that carboxamides of the formula (V)

are reacted with compounds of the formula (X)

in which the X radical is a halogen atom to give a carboxamide of the formula (XI)


4. The process as claimed in any one of claims 1 to 3, characterized in that the metal catalyst is selected from palladium and copper catalysts.
 5. The process as claimed in any one of claims 1 to 4, characterized in that at least one copper compound in catalytic amounts is used in the presence of a ligand.
 6. The process as claimed in any one of claims 1 to 5 using a base.
 7. The process as claimed in claim 5, wherein the ligands used are diamines.
 8. A compound of the formula (III)

in which R¹ is hydrogen, halogen, —CR′(CF₃)₂ where R′=hydrogen, fluorine or O—C₁₋₄-alkyl, and R² is —CH(Me)—CH₂—CHMe₂, —CH₂—CH₂-t-But or R¹ is halogen, —CR′(CF₃)₂ where R′=hydrogen, fluorine or O—C₁₋₄-alkyl, and R² is

and X is a halogen atom.
 9. A compound as claimed in claim 8 of the formula (IX)

in which X is a halogen atom.
 10. A compound of the formulae (IV) to (VI)


11. The use of at least one compound as claimed in any one of claims 8 to 10 in a process as claimed in any one of claims 1 to
 7. 